Cadmium(II) complexes with pyridine/dicarboxylic acid ligands as promising molecules for the treatment of oral candidiasis

Diana Liz Jimenez; Débora Taisa Keller da Silva; Talita da Paz Costa Sauda; Adriana Araújo de Almeida-Apolonio; Emanuele P O Roque; Pamella Fukuda de Castilho; João Víctor de Andrade Dos Santos; Sidnei M Silva; Lucas Pizzuti; Amilcar M Junior; Victor M Deflon; Kelly Mari Pires de Oliveira; Gleison Antônio Casagrande

doi:10.1016/j.jinorgbio.2025.112980

Cadmium(II) complexes with pyridine/dicarboxylic acid ligands as promising molecules for the treatment of oral candidiasis

J Inorg Biochem. 2025 Jun 26:271:112980. doi: 10.1016/j.jinorgbio.2025.112980. Online ahead of print.

Authors

Affiliations

¹ Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, 79804-970 Dourados, MS, Brazil.
² Grupo de Pesquisa em Síntese e Caracterização Molecular, Universidade Federal de Mato Grosso do Sul - Instituto de Química, 79074-460 Campo Grande, MS, Brazil.
³ Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, 79804-970 Dourados, MS, Brazil; Universidade Estadual do Mato Grosso do Sul, 79804-970 Dourados, MS, Brazil.
⁴ Departamento de Odontologia, Universidade Estadual de Maringá, 87083-240 Maringá, PR, Brazil.
⁵ Universidade de Caxias do Sul -UCS, 95070-560 Caxias do Sul, RS, Brazil.
⁶ Instituto de Química, Universidade Federal do Rio Grande do Norte, 59078-900, Av. Senador Salgado Filho, s/n, Natal, RN, Brazil.
⁷ Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil.
⁸ Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, 79804-970 Dourados, MS, Brazil; Faculdade de Ciências Biológicas e Ambientais, Universidade Federal de Grande Dourados, 79804-970 Dourados, MS, Brazil. Electronic address: kellyoliveira@ufgd.edu.br.
⁹ Grupo de Pesquisa em Síntese e Caracterização Molecular, Universidade Federal de Mato Grosso do Sul - Instituto de Química, 79074-460 Campo Grande, MS, Brazil. Electronic address: gleison.casagrande@ufms.br.

PMID: 40582267
DOI: 10.1016/j.jinorgbio.2025.112980

Abstract

Overgrowth of Candida spp., known for its strong adhesion to biotic and abiotic surfaces, makes treatment difficult in denture stomatitis. To address this challenge, two novel cadmium(II) complexes containing 2,5-pyridinedicarboxylic acid (H₂L) (complex 1 [Cd(HL)(H₂O)(DMSO)I]₂ and [Cd(HL)(H₂O)(bipy)I] complex 2), were synthesized and fully characterized by X-ray diffractometry, HRMS-ESI (+) spectrometry, ¹H and ¹³C NMR, FT-IR and elemental analysis. These complexes were evaluated for their antifungal, antibiofilm, hemolytic, and mutagenic properties. The interaction of these complexes with established antifungal agents was also investigated. Both complexes demonstrated remarkable antifungal activity, particularly against C. albicans and C. krusei, with MIC ranging from 62.5 (97.91 μM) to 0.48 (0.75 μM) μg/mL and MFC from 125 (195.82 μM) to 3.80 (5.95 μM) μg/mL. Furthermore, these complexes effectively inhibited C. krusei biofilm formation on prosthetic acrylic resin test specimens, with complex 2 showing superior activity. The complexes also displayed synergistic effects with fluconazole, furthermore, sorbitol assays have shown that cell wall is one of the targets of the tested complexes. Importantly, hemolysis assays indicated that the complexes were non-cytotoxic to human erythrocytes, and mutagenicity assays confirmed their non-mutagenic nature. These findings suggest that the synthesized cadmium(II) complexes, particularly complex 2, possess significant potential as therapeutic agents for the treatment of denture stomatitis and oral candidiasis in general.

Keywords: Antifungal activity; Candida albicans; Candida krusei; Prosthetic acrylic resin; Pyridinedicarboxylic acids.